Development of an economical fermentation platform for enhanced ansamitocin P-3 production in Actinosynnema pretiosum

Abstract

Background

Ansamitocin P-3 (AP-3), produced by Actinosynnema pretiosum, has extraordinary antitumor activity and has been used as toxic “warhead” in antibody-conjugated drugs. However, AP-3 production is limited by its low yield and thus the high cost of fermentation. In this study, we aimed to reduce fermentation costs by utilizing the low-cost substrates and improve the AP-3 production, simultaneously.

Result

In this study, low-cost substrates used for ansamitocins production were selected via single-factor experiments and then the concentrations of these suitable carbon and nitrogen sources were optimized by response surface method (RSM). Cane molasses, glycerol, and cold-pressed soybean powder were determined to be the most suitable economical carbon and nitrogen sources for AP-3 accumulation. The AP-3 titer in shaking flasks reached 111.9 mg/L using the optimized medium containing cane molasses (63.22 g/L), glycerol (22.91 g/L), and cold-pressed soybean powder (3.29 g/L). In addition, appropriate supplementation with isobutanol, soybean oil, and vitamin B₁ resulted in a marked enhancement in AP-3 production, to 141 mg/L. Meanwhile, the cost of this optimized fermentation medium was around 50% lower than those of two other high-yielding media.

Conclusion

Our findings provided practical and economically competitive cultivation conditions for the production of a value-added antitumor agent and may thus extend the applications of ansamitocin P-3.

Keywords

Ansamitocin P-3 / Cane molasses / Soybean powder / Medium optimization

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Funding

National Natural Science Foundation of China(21776081)